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Compelling Mifepristone Research - The Medical Uses of Mifepristone

In addition to its use in terminating unwanted pregnancies, MIFEPRISTONE (formerly known as RU-486) also may be effective in treating a range of serious diseases and medical conditions, many of which particularly affect women. Yet U.S. clinical trials for most of these uses have come to a standstill due to anti-abortion politics.

Abortion & Fertility Control

Available to women in many countries, mifepristone is the first in a new generation of fertility control agents that can terminate an early pregnancy. Mifepristone works by blocking the action of progesterone, which is necessary to sustain a pregnancy.

Mifepristone, taken along with a prostaglandin, has been used by millions of women worldwide and has found to be safe and effective as an early abortion method during the first nine weeks of a pregnancy.

A woman can take mifepristone as soon as she knows she is pregnant. Mifepristone is administered orally, is non-invasive, requires no anesthesia, and bears little risk of infection. Many women prefer mifepristone because the procedure is more private and allows them greater psychological control in ending a pregnancy. Administered with a single dose of a misoprostol (a prostaglandin given either orally or as a vaginal suppository), mifepristone has been proven to be highly effective in successfully terminating pregnancy. [1]

Studies also show that mifepristone is a safe, effective form of emergency contraception. [2] [3] Preliminary studies show, as well, that mifepristone can act as both a male and female contraceptive.


Meningiomas account for 15% of all primary brain tumors and 12% of all spinal cord tumors. Meningiomas occur two times more frequently in women than men. [4]

Meningiomas may enlarge or become symptomatic during the menstrual cycle or pregnancy, and are also associated with breast cancer. These indications suggest that the hormones estrogen and progesterone influence tumor growth. By binding with progesterone receptors, mifepristone may inhibit the growth of, or actually reduce meningiomas size.

In one study, mifepristone was found to have some efficacy in the treatment of patients with inoperable meningioma. [5] Another study showed that mifepristone interfered with the steroid action that influences the growth of meningiomas, further demonstrating mifepristone's treatment potential with this type of tumor. [6]

Meningioma patients have testified before Congress that mifepristone has helped them battle their disease. The Feminist Majority Foundation currently operates a Compassionate Use Program in which 33 meningioma patients, with special FDA approval, are being treated with mifepristone under their physician's care. Many of these patients report that mifepristone has eased their pain and suffering. Some have said the drug is saving their lives.

Endometriosis & Fibroid Tumors

Ten to twenty percent of American women of childbearing age have endometriosis. [7] Mifepristone shows promise as a treatment for endometriosis, which is a chronic, painful, long-term disease that can affect women throughout their entire reproductive years.

In addition to its anti-progestin and anti-glucocorticoid properties, mifepristone is a non-competitive anti-estrogen. As such, mifepristone blocks the capacity of the endometrial tissue to grow in response to estrogen, making mifepristone a possible hormonal treatment for endometriosis. [8]

Similarly, researchers believe mifepristone is a promising treatment option for uterine fibroid tumors. [9] Fibroid tumors, which are present in approximately 70% of women and cause symptoms in 25% , are a leading cause of the more than 600,000 hysterectomies performed annually in the U.S. [10]

In one recent clinical study, researchers found that mifepristone reduced the average size of uterine fibroid tumors by 50% within six months of low-dose mifepristone therapy and that the drug was well tolerated by the women who participated in the study. [11]

Breast & Ovarian Cancers

The American Cancer Society estimates 211,240 cases of breast cancer will be diagnosed in 1105, with 40,410 deaths expected. Since 1990, the death rate has declined steadily, the result of improved treatment and early detection . However, since 1987, breast cancer incidence has increased by 0.3% per year. Breast cancer continues to be the second leading cause of cancer death among women of all ages, and 2.3 million women living in the US have been diagnosed with breast cancer. [12]

Mifepristone is an anti-progestin, which blocks the action of progesterone, and may be effective in treating progesterone-dependent forms of breast cancer. [13] [14] Experts estimate that mifepristone may be an effective treatment in 60% of breast cancer tumors, according to the National Surgical Adjuvant Breast and Bowel Project.

In animal studies in the Netherlands, mifepristone reduced breast cancer tumors as effectively as Tamoxifen, one of the most common and effective breast cancer treatments drugs. In that research, the administration of both Tamoxifen and mifepristone reduced tumors size more than each drug alone. [15]

A French clinical trial found that mifepristone might also be a treatment for tumors that have become resistant to Tamoxifen. In addition, this study reported that mifepristone reduced the pain caused by the metastasis of cancer cells to the bones. Trials have also been conducted in Canada and California to assess mifepristone as a treatment option for women who have breast cancer recurrences.

In 1100, ovarian cancer was diagnosed in approximately 23,000, and caused the death of more than 14,000 women. Ovarian cancer causes the most deaths of all gynecologic cancers and is responsible for five percent of all cancers in women. [16] A U.S. study reported in 1100 that for women with persistent ovarian cancer despite standard chemotherapy and radiation, treatment with mifepristone showed benefits in halting the disease in 26% of patients studied. [17]

Cushing's Syndrome, Psychotic Depression & The HIV Virus

Cushing's Syndrome results from an over-production of the cortisol hormone. Too much cortisol can be fatal. The vast majority of Cushing's Syndrome victims are women, primarily in their 20s to 40s. [18]

Some forms of the deadly Cushing's Syndrome can be treated with mifepristone.

The mifepristone compound is an anti-glucocorticoid: it binds to glucocorticoid receptors in the body and prevents the cortisol from binding. One important National Institutes of Health (NIH) study has shown that when persons gravely ill with inoperable Cushing's Syndrome tumors, more than 50% experienced reversal and control of the disease as well as complete regression of the Syndrome's physical features. [19]

Mifepristone has already helped patients suffering from advanced Cushing's Syndrome. Two of those survivors testified before Congress in 1990 that mifepristone saved their lives. [20]

Some studies indicate that the cortisol hormone plays a key role in the replication of the HIV virus. Elevated serum cortisol has been found at all stages of HIV-infection, particularly in late-stage HIV (AIDS) patients.

The anti-glucocorticoid properties of mifepristone make it a possible treatment for HIV and other cortisol related conditions and diseases. One in vitro study showed that by blocking cortisol, mifepristone lessened the infectivity of HIV and reduced the production of HIV by the already infected cells by 70%. [21]

As an anti-glucocorticoid, mifepristone is proving to be effective in treating several additional conditions and diseases that are caused by elevated levels of cortisol. These health problems include depression [22] , alcoholism, substance abuse, anorexia nervosa, ulcers, diabetes, Parkinson's, multiple sclerosis, and Alzheimer's. [23] Acute Psychotic Depression, which is manifest in 15% of patients with severe generalized depression causes symptoms such as hallucinations and paranoia. It is a disease for which no easy or readily effective treatment presently exists or is FDA approved. Patients are typically treated with either electric shock therapy (which carries considerable stigmatization), or dual drug therapy with anti-psychotic and anti-depressant medications. Unfortunately, both treatments can take weeks to months to have any significant effect.

Because mifepristone can rapidly bring down the elevated cortisol levels associated with this form of depression, researchers at Stanford have been conducting clinical trials treating acute psychotic depression patients with mifepristone and the results have been very successful. Alan Schatzberg, MD, Chair of Stanford's psychiatry department likens mifepristone to "the equivalent to shock therapy in a pill" because in more than two-thirds of patients who took medium or high doses showed significant reductions in psychotic symptoms within seven days. [24] Because of these results, the U.S. Food and Drug Administration has put mifepristone on fast-track approval as a treatment for psychotic depression-it is the first drug for a psychiatric condition to be fast-tracked. [25]

Uterine Fibroids and Mifepristone

Uterine fibroids are non-cancerous or benign tumors that arise from the muscular wall of the uterus. Approximately 70 percent of all women have fibroids [26] and 25 percent of those women have symptoms due to the presence of fibroids.[27] Fibroids develop in women of all "races" yet for some unknown reason they are two to three times more prevalent among African American women. [28] Fibroids remain the single most common indication for hysterectomy in the United States, accounting for approximately 30 percent of the 600,000 hysterectomies performed in the U.S. annually, at an estimated expense of greater than one billion dollars per year.[29]

Uterine fibroids, also known as myomas, tend to become more symptomatic as women age with the peak incidence for hysterectomies due to fibroids occurring around age 45.[28] The major symptoms associated with fibroids are heavy menstrual bleeding (causing anemia in many cases), pelvic pain, pain during sex and a frequent need to urinate. Fibroids can sometimes cause problems becoming pregnant and maintaining a pregnancy. Fibroid growth seems to be dependent on hormonal fluctuations. Fibroids have been observed to grow rapidly during pregnancy and they often shrink after menopause when hormone levels decrease considerably.


Medical (drug) treatment has consisted largely of Lupron, a hormonal treatment that essentially induce a menopausal state. By stopping the hormonal fluctuations that induce periods, Lupron temporarily causes a significant reduction in the size of the fibroids and also can prevent the anemia associated with the excessive fibroid-related menstrual bleeding.[28] While it is the most common medical treatment for fibroids, Lupron has not been approved by the FDA to reduce fibroid size. Rather, doctors use it "off-label" in attempt to shrink uterine fibroid size and improve anemia prior to fibroid-related surgery. Lupron is administered in a monthly shot or taken as a nasal spray. Side effects include significant hot flashes and diminished bone mineral density. This bone loss can take up to two years to be restored after treatment with Lupron.[30]

Surgical and interventional radiology treatment options are more plentiful than medical options. Options include[27] :

  • Hysterectomy: Removal of the entire uterus (with or without removing ovaries).
  • Myomectomy: Removal of the fibroid/s while preserving the uterus.
  • Fibroid Myolosis: Similar to myomectomy but the fibroid is zapped with electricity which constricts the blood vessels and cuts off the blood supply to the fibroid.
  • Endometrial ablation: Removal of the uterine lining with our without myomectomy. This helps stop excessive bleeding but doesn't treat many symptoms due to fibroid size.
  • Uterine-artery Embolization: Performed by an interventional radiologist, the uterine artery supplying blood to the fibroid is blocked causing it to shrink. This is somewhat similar to fibroid myolosis.

At a rate of 5.6 per 1000 women, the U.S. hysterectomy rate is three to four times higher than that of most European countries, Australia and New Zealand [31]. Only 11 percent of hysterectomies are performed because of cancer [32]. According to the American College of Obstetricians and Gynecologists, the U.S. rate of hysterectomy did not change significantly from 1990 to 1997 with hysterectomy remaining the most common nonpregnancy-related surgical procedure in the United States [31].

A recent study presented at the Society of Cardiovascular and Interventional Radiology meeting stated that in a head-to-head comparison with hysterectomy, uterine artery embolization, a "minimally-invasive" procedure is as effective as hysterectomy in treating fibroids [33]. The study results are being submitted to the FDA in order to approve uterine artery embolization as a safe and effective treatment for fibroids. Studies presented at the conference highlighted the unfortunate fact that most gynecologists do not tell their patients about this less invasive procedure, or they tell them only negative aspects of the procedure. Women undergoing the procedure had usually heard of it from friends or newspaper articles. Part of the problem may be that because the embolization procedure is performed by a radiologist, many gynecologists do not know of the procedure or do not know enough about it [33].

Despite the medical or more invasive fibroid treatments, uterine fibroids frequently reappear even after surgical or medical therapy. After stopping hormonal medications, fibroid size usually returns to pre-treatment levels within several months and the long-term recurrence rate 10 years after myomectomy is 27 percent [34]. Clearly, less invasive treatments with fewer side effects need to become available. The Feminist Majority Foundation believes that mifepristone is a critical option for women that must be further studied.


Studies with mifepristone, a drug that blocks the effects of the hormone progesterone, indicate that when compared to the present medical standard of care, Lupron, three months of mifepristone was as effective as six months of Lupron in causing a 50 percent shrinkage in fibroid size [35]. Moreover, it was much better tolerated, causing minimal hot flashes. Furthermore, because it doesn't suppress estrogen levels as Lupron does, mifepristone does not cause loss of bone density. Additionally, mifepristone is approximately 1/7th the cost of Lupron!

Larger clinical trials validating mifepristone's effectiveness and safety in treating fibroids have been brought to a standstill due to anti-abortion politics. The Feminist Majority Foundation has launched the "Mifepristone and Women's Health" campaign, calling for more clinical trials exploring mifepristone's medical potential in treating numerous conditions that primarily affect women: breast cancer, uterine cancer, ovarian cancer, endometriosis, and uterine fibroids. Fibroid research with mifepristone is critical in providing women with a better tolerated, safe and effective non-surgical alternative in the management and treatment of fibroid tumors. The Feminist Majority Foundation fully supports Senator Jean Carnahan and her co-sponsors, Senators Barbara Mikulski (D-MD) and Jim Jeffords (I-VT) in pushing for more research on uterine fibroids and we ask that further clinical trials with mifepristone be a vital part of that research. Show your support for legislation that would increase funding for uterine fibroid research: Take Action Today!


[1] Spitz IM, et al. Early pregnancy termination with mifepristone and misoprostol in the United States. New England J of Medicine, 4/30/98.

[2] Baird DT, Dewar M, Glasier A et al. Mifepristone (RU486) compared with high-dose estrogen and progestogen for emergency postcoital contraception. New England J of Medicine, 10/8/92.

[3] Bygdeman M, Danielsson KG, et al. Contraceptive use of antiprogestin. European J of Contraception and Reproductive Health Care, 6/99.

[4] Association for Brain Tumor Research.

[5] Grunberg SM, et al. Role of antiprogestational therapy for meningiomas. Human Reproduction, 1994.

[6] De-Motta LA, de-Motta LD. Endocrine treatment of meningiomas: a review. Arq-Neuropsiquiatr. 6/95.

[7] Endometriosis Alliance.

[8] Kettel M, Murphy AA, et al. Clinical efficacy of the antiprogesterone RU-486 in the treatment of endometriosis and uterine fibroids. Human Reproduction, 1994.

[9] Eldar-Geva T; Healy DL . Other medical management of uterine fibroids. Baillieres Clin Obstet Gynaecol, 6/12/98.

[10] American College of Obstetricians and Gynecologists.

[11] Eisinger, Meldrum, et al. Low-Dose Mifepristone for Uterine Leiomyomata, Journal of the American College of Obstetricians and Gynecologists, February 1103.

[12] American Cancer Society. Breast Cancer Facts and Figures 1105-1106, 9/22/05.

[13] Martin JH, et al. Reduced expression of endothelial and inducible nitric oxide synthase in a human breast cancer cell line which has acquired estrogen independence. Cancer Letters, 9/20/99.

[14] Norris JD, Paige LA et al. Peptide antagonists of the human estrogen receptor. Science, 7/30/99.

[15] Klijn JGM, et al. Pre-clinical and clinical treatment of breast cancer with antiprogestins. Human Reproduction, 1994.

[16] Centers for Disease Control and Prevention.

[17] Rocereto, T. et al. Phase II study of Mifepristone in Refractory Ovarian Cancer. Gynecologic Oncology, 1100.

[18] Cushing's Syndrome Association.

[19] Nieman LK et al. Successful treatment of Cushing's Syndrome with the glucocorticoid antagonist RU-486. J of Endocrinology and Metabolism. 1985.

[20] U.S. House of Representatives, Subcommittee on Regulation, Business Opportunities, and Energy, Committee on Small Business. RU-486: The import ban and its effects on medical research. 11/19/90.

[21] Weiner et al. The glucocorticoid receptor type II complex is a target of the HIV-1 vpr gene product. Proc. Natl. Acad. Science, USA, 4/95.

[22] Wolkowitz OM, Reus VI. Treatment of Depression with antiglucocorticoid drugs. Psychosomatic Medicine, 9/99.

[23] Wolkowitz OM, Reus VI. Treatment of Depression with antiglucocorticoid drugs. Psychosomatic Medicine, 9/99.

[24] Wolkowitz OM, Reus VI. Treatment of Depression with antiglucocorticoid drugs. Psychosomatic Medicine, 9/99.

[25] Wolkowitz OM, Reus VI. Treatment of Depression with antiglucocorticoid drugs. Psychosomatic Medicine, 9/99.

[26] National Institutes of Health; National Institute of Environmental Health Sciences

[27] Stewart, E. MD, Lancet; "Seminar in Uterine Fibroids", 1101;357:293-298

[28] Speroff, L. MD, Glass, R. MD, Kase, N MD, Clinical Gynecologic Endocrinology and Infertility, Lippincott Williams and Wilkins, 1999. p.149.

[29] American College of Obstetricians and Gynecologists. "Uterine Leiomyomata. ACOG Technical Bulletin No. 192. Washington DC: American College of Obstetricians and Gynecologists, 1994.

[30] Speroff. p.1067.

[31] ACOG News Relase, January 31, 1102

[32] CDC website. August 8th, 1997. "Special focus: Surveillance for Reproductive Health; Hysterectomy Surveillance-U.S."

[33], April 9, 1102

[34] Speroff. p.151.

[35] Murphy, A MD, Kettle, M MD, et al, "Regression of Uterine Leiomyomata in Response to the Antiprogesterone RU-486", Journal of Clinical Endocrinology and Metabolism, Vol. 76, No. 2, 1993